Penetration of phospholipid monolayers by opioid peptides and opiate drugs (agonists and antagonists)

The monomolecular film technique was used to compare the specific interaction of opioid peptides (Leu-enkephalin, Met-enkephalin, dynorphin A and β-endorphin) and opiate agonists (alkaloids such as levorphanol and ethylketocyclazocine) and opiate antagonists (naloxone and diprenorphine) with various phospholipid films (phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine and dioleoylphosphatidylglycerol). We were able to demonstrate the interaction of opiate drugs and opioid peptides (0.1 μM) with both zwitterionic and negatively charged phospholipids up to very high surface pressures. In the presence of a phospholipid monolayer, the surface activity of opioid peptides became much greater than that observed at the air-water interface. In the case of opiate drugs, the phenomenon was different and these drugs penetrate the monolayer films at a low pressure in comparison with opioid peptides, even at very high concentration. We have also evaluated the penetration of the antagonists naloxone and diprenorphine; the interaction of these was very low. © 1993.